A systematic study of the effects of chronic ethanol ingestion on the metabolism of prostaglandins and related compounds is proposed. Previous research has indicated that ethanol consumption influences both the synthesis and degradation of prostaglandins. In order to determine a cause and effect relationship, it is proposed to investigate the effect of the intensity and duration of ethanol exposure on prostaglandin metabolism. Parameters to be assayed include the influence of ethanol on the synthesis of prostaglandins E2 (PGE2) and F2 alpha (PGF2 alpha), thromboxanes and prostacyclin; the effect of ethanol on the enzymatic degradation of PGE2 and PGF2 alpha; the effect of ethanol on substrate (arachidonic acid) availability; and the possible interaction between ethanol, prostaglandins and cyclic nucleotides. The research will use the guinea pig chronically dosed with ethanol via a liquid diet as a model. Synthesis of prostaglandins, thromboxanes and prostacyclin will be assayed by radiochemical methods. The degradation of PGE2 and PGF2 alpha by tissue homogenates will be followed isotopically using thin layer chromatography for the separation of the reaction products. Gas liquid chromatography will be used to measure substrate availability and radioimmune assays will be used to determine cyclic nucleotide levels. Differences observed in enzymatic activity will be further studied to determine the mechanism of such changes. Parameters to be studied include kinetic determination of Km and Vmax values and the availability of appropriate cofactor(s). Such studies will provide a starting point for the treatment of pathophysiology related to changes in prostaglandin metabolism as the result of ethanol consumption.